Amacrine cells are laterally-oriented interneurons in the proximal retina which are located strategically to influence the response properties of ganglion cells. Thus, amacrine cells play a key role in determining the visual information carried by the final output pathway of the retina to higher brain centers. Although retinal amacrine cells have been the subject of numerous morphological and pharmacological studies, much of our knowledge of amacrine cell function in the mammal has been attained indirectly from work directed at ganglion cells or inferred from studies of lower vertebrates. The vast majority of retinal neurotransmitters, including peptides, are used by amacrine cells to affect ganglion cell activity. It is likely, then, that retinopathies derived from imbalances of neurotransmitters would be localized to circuitry subserved by amacrine cells. Unfortunately, the physiology of amacrine cells, and thus the function of many of these transmitters, is presently unclear. The long term goal of this research is to determine the physiological response properties expressed by amacrine cells in the mammalian retina and to correlate these with their morphologies. The experimental strategy is not only to determine the correlations that exist between amacrine cell structure and function but also to form a physiological framework to incorporate the available morphological and pharmacological data. The basic method used is intracellular recording from neurons in the superfused, retina-eyecup preparation of the rabbit. Physiologically-characterized cells are subsequently labeled with intracellular stains such as horseradish peroxidase (HRP) to determine their soma-dendritic morphologies. Recent findings indicate that amacrine cells show a much richer variety of responses than thought previously, such as orientation and direction sensitivity. Thus, the specific aims of the proposed research focus on complex response properties of amacrine cells and their generation. These include: (1) To determine the direction sensitivity of the cholinergic starburst amacrine cells and the mechanism underlying its generation. (2) To examine electrical coupling between the orientation-sensitive Ae-type horizontal cells and between the orientation-biased amacrine cells in the rabbit. This line of research will establish whether electrical synapses preserve and expand the orientation sensitivity of these cells across their extensive receptive fields. (3) To study the orientation sensitivity of bipolar cells in the rabbit to determine if they may provide the route for passage of orientation-sensitive visual information from horizontal to amacrine cells. (4) To examine the role of active propagation of synaptic inputs in shaping the receptive fields of amacrine cells.